title: Smurf1 ubiquitin ligase targets Kruppel-like factor KLF2 for ubiquitination and degradation in human lung cancer H1299 cells.
abstract: Krüppel-like factor 2 (KLF2) has been demonstrated to be essential for normal lung development, erythroid differentiation, T-cell differentiation, migration and homing. However, the mechanisms underlying the regulation of KLF2, in particular its responsible E3 ligase is still unclear. Here we show that the homologous to E6AP carboxyl terminus (HECT)-type ubiquitin ligase Smad ubiquitination regulatory factor 1 (Smurf1) interacts with and targets KLF2 for poly-ubiquitination and proteasomal degradation specifically in lung cancer H1299 cells. The catalytic ligase activity of Smurf1 is required for it to regulate KLF2. Consequently, Smurf1 represses the transcriptional factor activity of KLF2 and regulates the expression its downstream genes such as CD62L and Wee1. This study provided the first evidence that Smurf1 functions as an E3 ligase to promote the ubiquitination and proteasomal degradation of KLF2.
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.forename: Shan
authors.initials: S
authors.lastname: Shen
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Wang
authors.forename: Guichun
authors.initials: G
authors.lastname: Xing
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Yin
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D025941:Protein Interaction Mapping; D015533:Transcriptional Activation; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; C498342:SMURF1 protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex